scholarly journals Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 546
Author(s):  
Wim Verlinden ◽  
Eugénie Van Mieghem ◽  
Laura Depauw ◽  
Thomas Vanwolleghem ◽  
Luisa Vonghia ◽  
...  
Keyword(s):  
Liver Function ◽  
Liver Steatosis ◽  
Potential Candidate ◽  
Aminopyrine Breath Test ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
High Prevalence ◽  
Microsomal Liver ◽  
Invasive Method ◽  
Aggressive Clinical Course

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice.

scholarly journals LncRNA NEAT1/microRNA-129-5p/SOCS2 axis regulates liver fibrosis in alcoholic steatohepatitis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Junfeng Ye ◽  
Yuanqiang Lin ◽  
Ying Yu ◽  
Di Sun
Keyword(s):  
Liver Fibrosis ◽  
Liver Function ◽  
Inflammatory Factors ◽  
Cytokine Signaling ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Inflammation Reaction

Abstract Background Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to play an essential role in non-alcoholic fatty liver disease. However, the role of NEAT1 in regulation of alcoholic steatohepatitis (ASH) remains largely unknown. This study aims to explore the role of NEAT1 in ASH by mediating microRNA-129-5p (miR-129-5p) targeting suppressor of cytokine signaling 2 (SOCS2). Methods NEAT1, miR-129-5p and SOCS2 expression in serum of ASH patients were assessed. In the in vitro cellular experiment, we transfected siRNAs, oligonucleotides or plasmids into ethanol-induced AML-12 mouse hepatocytes to alter NEAT1 and miR-129-5p expression, and inflammatory factors and lipid content were determined. In the in vivo animal experiment, we injected lentiviruses carrying siRNAs, oligonucleotides or plasmids onto ASH mice (ASH induced by feeding mice a Lieber-DeCarli ethanol diet) to alter NEAT1 and miR-129-5p expression through the tail vein. Serum liver function, blood lipids and inflammatory factors were detected; liver histopathology, liver cell apoptosis, and fibrosis were observed. The relationship between NEAT1 and miR-129-5p, or between miR-129-5p and SOCS2 was verified. Results MiR-129-5p was reduced while NEAT1 and SOCS2 were elevated in ASH. Inhibited NEAT1 or elevated miR-129-5p suppressed the elevated lipid metabolism and restrained inflammation reaction in ethanol-stimulated AML-12 cells. The promoted miR-129-5p and inhibited NEAT1 could improve the liver function and repress blood lipid, inflammation reaction, hepatocyte apoptosis and liver fibrosis in ethanol-induced ASH mice. Furthermore, NEAT1 could negatively regulate miR-129-5p to target SOCS2. Conclusion We have found that the inhibited NEAT1 could suppress liver fibrosis in ASH mice by promoting miR-129-5p and restraining SOCS2, thereby decelerating the development of ASH.

scholarly journals Influence of platelet-enriched plasma on the morpho-functional state of liver in rats with induced non-alcoholic steatohepatitis and dyslipidemia

2020 ◽  
Vol 10 (6) ◽  
pp. 455-464
Author(s):  
O. Appelhans ◽  
I. Maznichenko ◽  
O. Kasatkin ◽  
Abdulla Hussein ◽  
M. Biriuk ◽  
...  
Keyword(s):  
Functional State ◽  
Liver Steatosis ◽  
Atherogenic Diet ◽  
Pathological Examination ◽  
Atherogenic Dyslipidemia ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Group I ◽  
Alt Activity

Non-alcoholic steatohepatitis (NASH) is a consequence of the progression of non-alcoholic fatty liver disease (NAFLD), which can lead to cirrhosis or hepatocellular insufficiency. NAFLD is a predictor of cardiovascular diseases (CVD) development. The important factor of the latter development is atherogenic dyslipidemia, and this is a type of 20-80 % NASH patients. The objective: to study the effectiveness of platelet-enriched plasma (PRP) influence on the morpho-functional state of liver in rats with non-alcoholic steatohepatitis. Materials and methods. The study was carried out on 80 adult male Wistar rats. Animals were divided into three groups: I group - animals that received an atherogenic diet for 90 days (n=10);  II group - animals with simulated NASH and DL which received a normal diet for 30 days (n=30); III group - animals with simulated NASH and DL and PRP correction (n=30); group of intact animals (n=10). NASH was simulated by introducing an atherogenic diet, which consisted of lard and 50 g / kg of butter for 90 days. PRP was punctured in the tissue of liver, twice at 0.05 ml with 7 days interval. The animals were taken out of the experiment after 90 days of the atherogenic diet  and on the 30th day after its cessation or PRP injection. The indicators of body mass, liver mass index (LMI), lipogram, hepatic transaminases were determined, and the further pathological examination of the liver tissue was done. Results and discussion. On the 90th day of the atherogenic diet, the GH level was 3.19 ± 0.56 mmol/l, ALT activity was 118 ± 6.12 U/l, AST 86 ± 4.52 U/l, morphological signs of NASH were detected. On the 30th day, the lipid profile of group II rats did not have statistical differences from group I, in rats after correction of NASH with the use of  PRP the level of LLD decreased by 51%, ALT activity - by 54%, AST - by 51% compared to control group (p <0.05), morphologically revealed I - II degree steatosis, focal protein dystrophy. Conclusions. On the 90th day of an atherogenic diet NASH was formed in experimental animals. They had dyslipidemia, which progressed for at least 30 days while maintaining a usual diet. After correction with PRP the level of atherogenic lipoproteins was significantly decreased in rats with NASH and DL; the activity of liver enzymes was lower compared to the group with simulated NASH and DL and the group with progression of NASH and DL for 30 days, morphologically the decrease in liver steatosis and severity of protein dystrophy comparing with a group with simulated NASH and DL and a group with progressive NASH and DL was observed for 30 days.

scholarly journals The Specific NLRP3 Antagonist IFM-514 Decreases Fibrosis and Inflammation in Experimental Murine Non-Alcoholic Steatohepatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sandra Torres ◽  
Maximilian J Brol ◽  
Fernando Magdaleno ◽  
Robert Schierwagen ◽  
Frank E. Uschner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Portal Pressure ◽  
Liver Steatosis ◽  
Inflammatory Cells ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Markers Of Inflammation

Background and Aims: Activation of the inflammasome NLRP3 (NOD-, LRR- and pyrin domain containing 3) contributes to the development of non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH). Therefore, this study explored the therapeutic effects of a novel and selective NLRP3 antagonist in a murine dietary model of NASH.Methods: Groups of 12-week-old ApoE-/- mice were fed ad lib for 7 weeks with a methionine/choline deficient (MCD) and western diet (WD). After 3 weeks of diet-induced injury, mice were injected i. p. with the NLRP3 antagonist IFM-514 (100 mg/kg body weight) or vehicle (0.5% carmellose) every day, 5 days/week for a further 4 weeks. Several markers of inflammation, fibrosis and steatosis were evaluated. Whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed.Results: IFM-514 inhibited IL-1β production in mice challenged with 20 mg/kg lipopolysaccharide, and in mouse and human inflammatory cells in vitro. IFM-514 inhibited hepatic inflammation in the in vivo non-alcoholic steatohepatitis model assessed by H&amp;E staining and in the hepatic gene expression of inflammasome-related proinflammatory cytokines. This effect was associated with significant reduction in caspase-1 activation. Similarly, IFM-514 was efficacious in vivo in MDC-fed ApoE-/- mice, markedly reducing portal pressure, Sirius red staining and 4-hydroxyproline content compared to vehicle-treated mice. Moreover, IFM-514 significantly reduced hepatic steatosis in MCD-fed ApoE-/- mice, as evidenced by NAFLD scores, oil red O staining, hepatic triglycerides and gene expression. In WD treated animals, similar trends in inflammation and fibrosis were observed, although not sufficient IFM-514 levels were reached.Conclusion: Overall, IFM-514 reduced liver inflammation and fibrosis, with mild effects on liver steatosis in experimental murine NASH. Blocking of NLRP3 may be an attractive therapeutic approach for NASH patients.

scholarly journals Features of the course of non-alcoholic fatty liver disease in HIV-infected individuals

2020 ◽  
Vol 47 (2) ◽  
pp. 66-71
Author(s):  
V. A. Akhmedov ◽  
N. F. Mamedova ◽  
A. V. Verbanov ◽  
O. V. Gaus ◽  
O. V. Gaus
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Experimental Studies ◽  
Rapid Progression ◽  
People Living With Hiv ◽  
Alcoholic Fatty Liver ◽  
High Prevalence ◽  
Alcoholic Fatty Liver Disease

This article reflects the course of non-alcoholic fatty liver disease (NAFLD) in HIV-infected individuals. It is noted that long-term antiretroviral therapy and the use of D-drugs can explain the high prevalence of steatosis in this category of patients. The results of experimental studies that demonstrate the direct effect of HIV on liver steatosis by infection of stellate liver cells, stimulation of abnormal expression of SREBP-1 and PPARγ are considered. The role of HIV-mediated microbial translocation as one of the triggers for the development of non-alcoholic steatohepatitis (NASH), which contributes to chronic inflammation due to an increase in the permeability of the intestinal barrier to bacterial products and endotoxins, is noted. Data are presented confirming the high prevalence of the abnormal distribution of fat and visceral obesity (components of lipodystrophy syndrome) in a cohort of HIV-infected individuals. There was a high prevalence of steatosis and steatohepatitis in HIV-infected patients with lipodystrophy as compared with HIV-infected patients without lipodystrophy. Data showing the high prevalence of NASH in HIV-infected individuals are presented. A high rate of progression of NAFLD in a cohort of HIV-infected individuals was observed, regardless of the presence/absence of a combined viral infection (chronic hepatitis C). It has been established that the classic risk factors for NAFLD (high body mass index, dyslipidemia, metabolic syndrome) can contribute to the rapid progression of the disease in people living with HIV, compared with representatives of the general population.

scholarly journals THE EFFICACY OF ERADICATION OF SMALL INTESTINAL BACTERIAL OVERGROWTH IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

2017 ◽  
Vol 4 ◽  
pp. 34-41
Author(s):  
Sergiy Tkach ◽  
Olena Gubska ◽  
Tetiana Cheverda
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Small Intestinal ◽  
Alcoholic Fatty Liver Disease

Background. Emerging evidence suggests a strong interaction between the gut, gut microbiota and liver. Derangement of gut flora, particularly small intestinal bacterial overgrowth (SIBO), occurs in a large percentage of patients with non-alcoholic fatty liver disease (NAFLD) and plays an important role in its pathogenesis. Aim. Study of the frequency of SIBO in various forms of non-alcoholic fatty liver disease, as well as the possibilities of its pathomorphosis as a result of eradication of SIBO as a result of the use of rifaximin or multicomponent probiotic. Material and methods. There were investigated 125 patients with non-alcoholic fatty liver disease (70 men, 55 women aged 18 to 65 years, mean age 37±6.7 years) developed at obesity or type 2 diabetes mellitus, including 85 patients with liver steatosis (group1) and 40 patients with non-alcoholic steatohepatitis (group 2). Patients with concomitant SIBO (70 patients) was treated with rifaximin or multicomponent probiotic. As the main endpoints of the study, the frequency of achieving eradication of SIBO was evaluated (estimated from the results of a repeated H2-lactulose hydrogen test after treatment), as well as a decrease in the severity of liver steatosis by steatometry and a decrease / normalization of transaminase levels 3 months after the start of the treatment. Secondary endpoints included the change in BMI and the HOMA-IR index 3 months after the start of the treatment. Results. SIBO in patients with non-alcoholic fatty liver disease was significantly more frequent than in control (p <0.005), and in patients with non-alcoholic steatohepatitis – significantly more often than in patients with liver steatosis (80 % vs 47.1 %, P <0.01). Eradication of SIBO after use of rifaximin was recorded in 30 of 36 patients with non-alcoholic fatty liver disease (83.3 %), including 16 of 20 patients with steatosis (80 %) and 14 of 16 (87.5 %) patients with non-alcoholic steatohepatitis. In the group of patients taking multicomponent probiotics after treatment, eradication of SIBO was noted in 12 of 36 patients (33.3 %), including 7 patients with steatosis (35 %) and 5 patients (31.3 %) with non-alcoholic steatohepatitis Conclusion. The investigation shows that the eradication of small intestinal bacterial overgrowth has the positive influence on the natural course of NAFLD and use of rifaximine should be discussed as a perspective therapeutic strategy at this pathology

Processes exacerbating apoptosis in non-alcoholic steatohepatitis

2019 ◽  
Vol 133 (22) ◽  
pp. 2245-2264 ◽  
Author(s):  
Marta B. Afonso ◽  
Rui E. Castro ◽  
Cecília M. P. Rodrigues
Keyword(s):  
Molecular Mechanisms ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Intrinsic Signals ◽  
Alcoholic Steatohepatitis ◽  
Significant Public Health Concern ◽  
High Prevalence ◽  
Significant Public Health ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is a significant public health concern, owing to its high prevalence, progressive nature and lack of effective medical therapies. NAFLD is a complex and multifactorial disease involving the progressive and concerted action of factors that contribute to the development of liver inflammation and eventually fibrosis. Here, we summarize fundamental molecular mechanisms underlying the pathogenesis of non-alcoholic steatohepatitis (NASH), how they are interrelated and possible translation to clinical applications. We focus on processes triggering and exacerbating apoptotic signalling in the liver of NAFLD patients and their metabolic and pathological implications. Indeed, liver injury and inflammation are cardinal histopathological features of NASH, a duo in which derailment of apoptosis is of paramount importance. In turn, the liver houses a very high number of mitochondria, crucial metabolic unifiers of both extrinsic and intrinsic signals that converge in apoptosis activation. The role of lifestyle options is also dissected, highlighting the management of modifiable risk factors, such as obesity and harmful alcohol consumption, influencing apoptosis signalling in the liver and ultimately NAFLD progression. Integrating NAFLD-associated pathologic mechanisms in the cell death context could provide clues for a more profound understating of the disease and pave the way for novel rational therapies.

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